Tumor-associated alterations in caspase-14 expression in epithelial malignancies

Clin Cancer Res. 2005 Aug 1;11(15):5462-71. doi: 10.1158/1078-0432.CCR-04-2527.


Purpose: Caspase-14 is unique among caspase family proteases in that its proteolytic processing has been principally associated with epithelial cell differentiation rather than apoptosis or inflammation. We investigated caspase-14 expression in several types of human epithelial malignancy by immunohistochemistry, correlating results with stage, histologic grade, and patient survival.

Experimental design: Tumor-associated alterations in caspase-14 expression were observed for cervical, ovarian, breast, gastric, and colon cancers.

Results: In cervical (n = 445), ovarian (n = 91), and colon (n = 106) specimens, expression of caspase-14 was significantly reduced in cancers compared with normal epithelium. Decreases in caspase-14 immunopositivity correlated with the histologic progression of cervical cancer (P < 0.0001, ANOVA). In localized gastric cancers, caspase-14 immunostaining was significantly lower in poorly differentiated tumors compared with well-differentiated tumors (P = 0.02, Pearson's chi(2) analysis). Lower caspase-14 expression was associated with advanced clinical stage in ovarian cancer (P = 0.04, ANOVA) and with shorter overall survival among ovarian cancer patients with serous tumors (n = 62) in both univariate (P = 0.005) and multivariate (P = 0.03) analysis. Lower caspase-14 expression correlated with shorter overall survival among patients with T(3)N(0)M(0) stage gastric cancers (n = 94; P = 0.006, log-rank test). In contrast to cervical, ovarian, and colon cancers, caspase-14 expression was increased in ductal carcinoma in situ and invasive cancers compared with normal mammary epithelium (P = 0.001, t test).

Conclusions: The findings reveal tumor-specific alterations in caspase-14 expression and suggest that differences in its expression may define subsets of epithelial cancers with distinct clinical behaviors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Caspase 14
  • Caspases / genetics*
  • Caspases / metabolism*
  • Cell Differentiation
  • Cell Line, Tumor
  • Colonic Neoplasms / pathology
  • Disease Progression
  • Female
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Microsatellite Repeats
  • Neoplasms, Glandular and Epithelial / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / pathology
  • Proportional Hazards Models
  • Stomach Neoplasms / pathology
  • Time Factors
  • Uterine Cervical Neoplasms / pathology


  • Biomarkers, Tumor
  • CASP14 protein, human
  • Caspase 14
  • Caspases